This grant proposal is directed towards extending our understanding of chromatin structure and function. We have placed a major emphasis on trying to understand the role of histone acetylation. Histone acetylation changes certain highly specific aspects of chromatin structure and we need to analyze the chemical basis for these changes. One change we have observed is a dramatic increase in solubility of hyperacetylated, high molecular weight chromatin. This gives us an opportunity to isolate specific DNA sequences associated with acetylated histones and to ask questions about their nature and whether these sequences are enriched in active genes. Additional procedures for fractionating chromatin into active and inactive material will be refined and tested. Various in vitro reconstituted nucleo-proteins will be prepared, assayed and utilized to test some of our basic hypotheses concerning the function of histone acetylation in transcription and in chromatin structure.